Isovitexin Depresses Osteoarthritis Progression via the Nrf2/NF-κB Pathway: An in vitro Study.
Isovitexin Depresses Osteoarthritis Progression via the Nrf2/NF-κB Pathway: An in vitro Study.
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DOI：
10.2147/jir.s299557
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发表时间：
2021
影响因子：
4.5
通讯作者：
Wan Q
中科院分区：
文献类型：
--
作者：
Hu X;Li R;Sun M;Kong Y;Zhu H;Wang F;Wan Q
骨关节炎（OA）是一种多因素的关节疾病，炎症过程有助于关节破坏。异牡荆素（IVX）是一种黄酮成分，存在于西番莲、大麻和棕榈中，以其抗炎特性而闻名。本研究在体外研究了IVX在OA发育调控中的作用及其潜在机制。通过CCK-8测定IVX对软骨细胞活力的影响。采用qPCR、Western blot和ELISA检测细胞外基质（ECM）变性和炎症表型；免疫荧光和Western blot检测NF-κB通路。通过分子对接预测IVX的相互作用蛋白，同时通过sirna敲低Nrf2来确认其作用。我们证明了IVX抑制了il -1β处理的软骨细胞的ECM变性和促炎因子。此外，IVX对il -1β暴露的软骨细胞中NF-κB信号传导的影响；从机制上讲，在分子对接和敲低研究中也证明了IVX可能与Nrf2结合抑制NF-κB通路。我们的数据表明，IVX通过Nrf2/NF-κB轴阻止OA疾病进展，这表明IVX有可能成为OA治疗的靶点。
Osteoarthritis (OA) is a multifactorial joint disease and inflammatory processes contribute to joint destruction. Isovitexin (IVX) is a flavone component found in passion flower, Cannabis and, and the palm that is known for its anti-inflammatory properties. This study investigated in vitro the role and underlying mechanism used by IVX in its regulation of OA development. Effects of IVX on the viability of chondrocytes were measured by CCK-8 assays. The phenotypes of extracellular matrix (ECM) degeneration and inflammation were measured by qPCR, Western blot, and ELISA; and NF-κB pathway was detected by immunofluorescence and Western blot. Molecular docking was applied to predict the interacting protein of IVX, while Nrf2 was knocked down by siRNAs to confirm its role. We demonstrated that IVX suppressed ECM degeneration and suppressed pro-inflammatory factors in IL-1β-treated chondrocytes. Additionally, IVX impact on NF-κB signaling in IL-1β-exposed chondrocytic cells; Mechanistically, it was also demonstrated in molecular docking and knock down studies that IVX might bind to Nrf2 to suppress NF-κB pathway. Our data suggest that IVX halts OA disease advancement through the Nrf2/NF-κB axis, suggesting a possibility of IVX as a target for OA therapy.